Continuous Subcutaneous Insulin Injection (SCII)
Medical treatment of several illnesses requires continuous drug infusion into various body compartments, such as subcutaneous and intra-venous injections. Diabetes mellitus (DM) patients, for example, require administration of varying amounts of insulin throughout the day to control their glucose levels. In recent years, ambulatory portable insulin infusion pumps have emerged as a superior alternative to multiple daily syringe injections of insulin, initially for Type 1 diabetes patients (Diabetes Medicine 2006; 23(2):141-7) and consecutively for Type 2 diabetes patients (Diabetes Metab 2007 Apr. 30, Diabetes Obes Metab 2007 Jun. 26). These pumps, which deliver insulin at a continuous basal rate as well as in bolus volumes, were developed to liberate patients from repeated self-administered injections, and allow them to maintain a near-normal daily routine. Both basal and bolus volumes must be delivered in precise doses, according to an individual prescription since an overdose or under-dose of insulin could be fatal.
The first generation of portable infusion pumps concerns “pager-like” devices with a reservoir contained within the device's housing. These devices are provided with a long tube for delivering insulin from the pump attached to a patient's belt to a remote insertion site. Both basal and bolus deliveries in these “pager-like” devices are controlled via a set of buttons provided on the device. A user interface means including a screen are provided on the device's housing for advising the user regarding fluid delivery status, programming flow delivery, alerts and alarms. Such devices are disclosed, for example, in U.S. Pat. Nos. 3,771,694, 4,657,486 and 4,498,843. These devices represent a significant improvement over multiple daily injections (MDI), but nevertheless, they are large sized, heavy, have long delivery/infusion tubing and lack discreetness, which substantially disturb daily activity.
To avoid the consequences of a long delivery tube, a new concept was proposed, which was implemented in second generation pumps. As described in prior art, this new concept concerns a remote controlled skin adherable device having a housing, a bottom surface adapted to be in contact with the patient's skin, a reservoir disposed within the housing, and an injection needle adapted for communication with the reservoir. In these second generation pumps, the user interface means are configured as a separate remote control unit that contains operating buttons and screen providing fluid delivery status, programming flow delivery, alerts and alarms, as described, for example, in U.S. Pat. Nos. 5,957,895, 6,589,229, 6,740,059, 6,723,072, and 6,485,461. These second generation devices also have several limitations, such as being heavy, bulky, and expensive because the device should be disposed of every 2-3 days (due to insertion site infections and reduced insulin absorption). Another significant drawback of these second generation skin adherable devices is associated with the remote controlled drug administration. The user is totally dependent on the remote control unit. For example, the user cannot initiate bolus delivery or operate the device if the remote control unit is not at hand, if it is lost or if it malfunctions.
A third generation of skin adherable infusion devices was devised to avoid the cost issues associated with the second generation devices and to extend patient customization. An example of such a device was described in U.S. Patent Application Publication No. 2007-0106218 and in International Patent Application Publication No. WO2007/052277. This third generation device contains a remote control unit and a skin securable (e.g., adherable) device/patch unit that may include two parts: (1) a reusable part containing at least a portion of the driving mechanism, the electronics, and other relatively expensive components, and (2) a disposable part containing the reservoir and in some embodiments at least one power source (e.g., a battery).
This third generation concept provides a cost-effective, skin securable infusion device and may allow diverse usage such as various reservoir sizes, various needle and cannula types.
A fourth generation of infusion devices was devised as a dispensing unit that can be disconnected and reconnected from and to a skin adherable cradle unit, as disclosed, for example, in U.S. Patent Application Publication No. 2008-0215035 and International Patent Application Publication No. WO2008/078318. Such skin-securable dispensing units can be operated using a remote control and/or a user interface (e.g., a button-based interface) provided on a housing of the dispensing unit, as disclosed, for example, in International Patent Application Publication No. WO2009/013736 [also published as U.S. Patent Application Publication No. 2010-0204657], and International Patent Application Publication No. WO2009/016636 [also published as U.S. Patent Application Publication No. 2010-0145276], filed Jul. 31, 2008, claiming priority to U.S. Provisional Application Ser. Nos. 60/963,148 and 61/004,019, and entitled “Portable Infusion Device Provided with Means for Monitoring and Controlling Fluid Delivery”, the disclosures of which are incorporated herein by reference in their entireties.
Continuous Glucose Monitoring (CGM)
Most diabetic patients measure their glucose levels several times during the day by obtaining finger-prick capillary samples and applying the blood to a reagent strip for analysis in a portable meter. While self-monitoring of glucose levels has had a major impact on improving diabetes care in the last few decades, the disadvantages of this technology are substantial and consequently leading to non-compliance. The drawbacks of this blood sampling technique are associated with discomfort of multiple skin pricking, inability to test the blood during sleep or when the subject is occupied (e.g., driving, running), and missing episodes of hyper- and hypoglycemia due to intermittent testing. A suggested glucose monitoring technology should therefore employ substantially automatic and continuous testing.
It is understood that there are three (3) techniques for continuously monitoring glucose in the subcutaneous interstitial fluid (ISF). The first technique is based on use of glucose oxidase based sensors as described in U.S. Pat. Nos. 6,360,888 to McIvor et al. and 6,892,085 to McIvor et al., both assigned to Medtronic MiniMed Inc. (CGMS, Guardian™ and CGMS Gold), and 6,881,551 to Heller et al., assigned to Abbott Laboratories, formerly TheraSense, Inc., (Navigator™). These sensors consist of a subcutaneously implantable, needle-type amperometric enzyme electrode, coupled with a portable logger.
The second technique is based on use of reverse iontophoresis-based sensors as detailed in U.S. Pat. No. 6,391,643 to Chen et al., assigned to Cygnus, Inc. (GlucoWatch™). A small current passed between two electrodes located on the skin surface draws ions and (by electro-endosmosis) glucose-containing interstitial fluid to the surface and into hydrogel pads incorporating a glucose oxidase biosensor (JAMA 1999; 282: 1839-1844).
The third technique, currently in clinical use, is based on microdialysis (Diab Care 2002; 25: 347-352), as detailed in U.S. Pat. No. 6,091,976 to Pfeiffer et al., assigned to Roche Diagnostics, as well as a marketable device (Menarini Diagnostics, GlucoDay™). In this technique, a fine, hollow dialysis fiber is implanted in the subcutaneous tissue and perfused with isotonic fluid. Glucose from the tissue diffuses into the fiber and is pumped outside the body for measurement by a glucose oxidase-based electrochemical sensor. Initial reports (Diab Care 2002; 25: 347-352) show good agreement between sensor and blood glucose readings, and good stability with a one-point calibration over one day.
Closed and Open Loop Systems
In an “artificial pancreas”, sometimes referred to as a “closed loop” system, an insulin pump delivers appropriate dosage of insulin according to continuous glucose monitor readings. An artificial pancreas avoids a human interface and is expected to eliminate debilitating episodes of hypoglycemia, particularly nighttime hypoglycemia. An intermediate step in the way to achieve a “closed loop” system is an “open loop” (or “semi-closed loop”) system also called “closed loop with meal announcement.” In this model, user intervention is required in a way similar to using of today's insulin pumps by keying in the desired insulin before they eat a meal. A closed loop system is discussed in U.S. Pat. No. 6,558,351 to Steil et al., assigned to Medtronic MiniMed. The system is comprised of two separate devices, a glucose monitor and an insulin pump which are adherable to two remotely body sites and the loop is closed by an RF communication link.
However, the Steil et al. closed loop system has some drawbacks. For example, the glucose monitor and insulin pump are two discrete components which require two insertion sites and two skin-pricking sites for every replacement of the insulin pump and the sensor, typically every 3 days. In addition, being separated apart, the two system components should be connected either by radio communication link or by wires. Moreover, the pump is heavy and bulky, with long tubing, making the system non-discreet and the system is extremely expensive since the pump infusion set and the monitor sensor require disposal every three (3) days.
Thus, it is desirable to provide a skin securable device which is configured for both drug (e.g., insulin) dispensing and continuous body analyte (e.g., glucose) level monitoring. It is also desirable to have such a device which is miniature, discreet, economical for the users and highly cost effective. An embodiment of such a desirable device is preferably connected to a single skin-insertable tip which preferably includes a subcutaneous cannula for delivering the drug to the body as well as a probe for monitoring the analyte via a single insertion site. Such a device is preferably disconnected from and reconnected to a skin adherable cradle unit, such that after connection of the patch to the cradle, current generated on the probe is delivered to the processor within a housing of the device.